As an extension of a project carried out over the past few years, studies will be continued on the isolation and characterization of an important group of enzymes termed transglutaminases that catalyzed the formation of covalent cross-links between protein molecules. Three distinct classes of these enzymes in guinea pig and human tissues and organs have been defined in this laboratory. The isozymic nature of these enzymes is under investigation. The presence of high concentrations of a transglutaminase in red blood cells of human and guinea pig is under further study. Of particular interest are the roles of the individual transglutaminases in blood coagulation, wound healing, seminal plasma coagulation during fertilization, cell membrane formation, cross-linking of hair proteins, keratin formation, and covalent attachement of biological amines in proteins. Biological control mechanisms, essential metal ion requirements, the immunochemical and the structural aspects of zymogen activation, active site and substrate specificities are under investigation. The biosynthesis, degradation and hormonal regulations of plasma protransglutaminase are currently under investigation.